3-Pyridinemethanamine → 3-methyl-5-(2-oxo-3-(4-(trifluoromethyl)benzyl)imidazolidin-1-yl)-N-(pyridin-3-ylmethyl)thiophene-2-carboxamide

HRID 560725Notes

Reaction equation

HRID 560725 reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([N:7]2[CH2:11][CH2:10][N:9]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=3)[C:8]2=[O:23])[S:4][C:3]=1[C:24](O)=[O:25].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)C(C)C)(C)C.[NH2:58][CH2:59][C:60]1[CH:61]=[N:62][CH:63]=[CH:64][CH:65]=1>CN(C)C=O.C(OCC)(=O)C>[CH3:1][C:2]1[CH:6]=[C:5]([N:7]2[CH2:11][CH2:10][N:9]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:21])([F:20])[F:22])=[CH:15][CH:14]=3)[C:8]2=[O:23])[S:4][C:3]=1[C:24]([NH:58][CH2:59][C:60]1[CH:61]=[N:62][CH:63]=[CH:64][CH:65]=1)=[O:25]

Participants

8

Reactant 5

HCID 310183-PyridinemethanamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 580315813-Methyl-5-(2-oxo-3-(4-(trifluoromethyl)benzyl)imidazolidin-1-yl)thiophene-2-carboxylic acid

Product 1

HCID 594812323-methyl-5-(2-oxo-3-(4-(trifluoromethyl)benzyl)imidazolidin-1-yl)-N-(pyridin-3-ylmethyl)thiophene-2-carboxamideYield 55%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred mixture of 3-methyl-5-(2-oxo-3-(4-(trifluoromethyl)benzyl)-imidazolidin-1-yl)thiophene-2-carboxylic acid (3.68 g, 9.56 mmol), 1-hydroxybenzotriazole (1.94 g, 14.36 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (2.75 g, 14.3 mmol) in N,N-dimethylformamide (40 mL) was added N,N-diisopropylethylamine (5.00 mL, 5.00 mmol), followed by the addition of 3-(aminomethyl)pyridine (0.97 mL, 9.57 mmol). The resulting reaction mixture was stirred for 16 h, then was diluted with ethyl acetate (300 mL). The organic layer was washed with saturated aqueous sodium bicarbonate solution (3×100 mL), water (100 mL) and brine (100 mL). The combined water/brine layer was extracted with dichloromethane (200 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by recrystallization from 50% ethyl acetate in hexanes to afford the title compound as a colorless solid (2.48 g, 55%): mp 102-104° C. (hexanes/ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 8.59 (s, 1H), 8.52 (s, 1H), 7.69 (d, J=7.8 Hz, 1H), 7.60 (d, J=8.0 Hz, 2H), 7.40 (d, J=8.0 Hz, 2H), 7.29-7.22 (m, 1H), 6.20 (t, J=5.6 Hz, 1H), 6.10 (s, 1H), 4.58 (d, J=5.6 Hz, 2H), 4.50 (s, 2H), 3.85-3.77 (m, 2H), 3.50-3.42 (m, 2H), 2.48 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 163.5, 155.8, 149.1, 148.7, 142.3, 141.4, 140.1, 135.5, 134.2, 130.1 (d, JC-F=32.6 Hz), 128.4, 125.7 (q, JC-F=3.8 Hz), 123.5, 122.1, 119.2, 112.5, 47.7, 42.7, 41.6, 41.1, 16.0; MS (ES+) m/z 475.3 (M+1).

Workup

  1. customThe resulting reaction mixture
  2. washThe organic layer was washed with saturated aqueous sodium bicarbonate solution (3×100 mL), water (100 mL) and brine (100 mL)
  3. extractionThe combined water/brine layer was extracted with dichloromethane (200 mL)
  4. dry with materialThe combined organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by recrystallization from 50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-1050cced9d59474ba1464f2554bc51c3
Source dataset
uspto-grants-2011_11
Patent number
US08063084B2

Reaction notes

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